Survival Of Patients Research Articles

Quality of life and survival in patients with uterine carcinosarcoma: A tertiary center observational study

Quality of life and survival in patients with uterine carcinosarcoma: A tertiary center observational study

Association of early tumor shrinkage with survival in patients with HER2-positive advanced gastric cancer treated with trastuzumab deruxtecan.

360 Background: Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate composed of an anti-human epidermal growth factor receptor 2 (HER2) antibody and a cytotoxic topoisomerase I inhibitor, has been approved as third or later-line treatment for unresectable HER2-positive advanced gastric cancer (AGC) based on the results of phase II DESTINY-Gastric 01 trial. However, there are few studies on real-world clinical outcomes and clinicopathological factors associated with efficacy of T-DXd in patients with HER2-positive AGC. Methods: This single-center retrospective study enrolled patients with AGC treated with T-DXd as third- or later-line chemotherapy between March 2018 and December 2023. Early tumor shrinkage (ETS) was defined as the relative change in the sum of longest diameters of RECIST target lesions at 8 ± 2 weeks compared with baseline. Prognostic outcomes were assessed using the log-rank test and Cox proportional hazards regression model. Results: A total of 57 patients were enrolled. The median age was 66 years (range, 31–82); 68% were male; 79% had HER2 3+; 23% had pulmonary metastasis; 67% were treated with T-DXd in the third-line setting. At a median follow-up of 27.6 months, the median progression-free survival (PFS) was 4.5 months (95% confidence interval [CI], 3.8–5.5), and the median overall survival (OS) was 7.3 months (95% CI, 4.9–9.4). Among 40 patients with target lesions, the overall response rate was 35.0% and the disease control rate was 90.0%. Patients with ETS had notably longer PFS (median PFS (months) 8.6 vs 4.1, P < 0.01) and OS (median OS (months) 9.1 vs 6.1, P < 0.01) than those without ETS. In multivariate analysis, ETS was associated with significantly longer PFS (hazard ratio [HR], 0.23; 95% CI, 0.08–0.63; P = 0.004) and OS (HR, 0.27; 95% CI, 0.12–0.65; P = 0.004), whereas pulmonary metastasis was associated with significantly shorter OS (HR 2.46, 95% CI, 1.07–5.65; P = 0.03). Conclusions: This study showed that achieving an ETS was significantly associated with a favorable prognosis in patients with HER2-positive AGC treated with T-DXd.

Outcomes of patients with peritoneal-limited metastatic gastric cancer (PLGC) undergoing bidirectional (BD) chemotherapy cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC).

328 Background: The prognosis of PLGC patients (pts) is poor with standard systemic therapy. PLGC pts who undergo CRS after BD chemotherapy (chemo) demonstrate prolonged survival. We retrospectively analysed the outcomes of pts who underwent BD chemo followed by CRS and HIPEC in a single institution, stratifying by peritoneal carcinomatosis index (PCI) and chemo regimen. Methods: PLGC pts who received BD chemo between January 2016 to September 2023 were enrolled and consented for data collection. BD chemo was either 3 weekly paclitaxel (PTX) (50mg/m2), S-1 (80mg/m2) and IP PTX (20mg/m2) or capecitabine (2g/m2), oxaliplatin (100mg/m2) (CAPOX) and IP PTX (40mg/m2). HIPEC utilised cisplatin 50mg/m2 at 40 for 60 minutes. Trastuzumab and nivolumab were given selectively. Pts without radiological progression after 24 weeks of BD chemo, with PCI7 and potential for complete resection underwent CRS including D2 gastrectomy and HIPEC. Post-resection, BD chemo was stopped. Survival was analysed by Kaplan Meier curves, adverse events (AEs) by CTCAE v5.0 and response by independent radiological review. Results: 34 pts were enrolled with median follow-up of 26.9 months (m). Median (range) age was 51 (17 – 79) and median PCI 12 (0-29). 52.9% were female, 8.8% had Cy1 only disease and 38% had prior gastrectomy. 3 out of 6 pts with evaluable disease had partial response. Median progression-free survival and overall survival (mOS) was 9.1m and 16.5m respectively. 7 pts (20.6%) underwent CRS with median (range) PCI of 1 (0-15.0). mOS in CRS vs non-CRS pts was 23.8m vs 14.6m (p=0.4); PCI <7 vs PCI ≥7 was 23.8m vs 14.6m (p=0.63); and CAPOX vs S1/PTX systemic chemotherapy was 23.9m vs 14.6m (p=0.29) respectively. Peritoneal cytology negativity increased from 25.8% to 86.4% after BD chemo. Peritoneal lesions biopsied post-BD chemo showed no tumour cells in 64% of cases. There was no treatment-related mortality. 1 pt had IP port removal due to complications. The commonest grade 3 AE was neutropenia (14.7%). Biomarker analysis is currently being performed. Conclusions: BD chemo CRS HIPEC was well tolerated with longer survival in patients undergoing CRS. Evaluation of tumour using PCI post-BD chemo may be sub-optimal.

Comparison between neoadjuvant chemotherapy followed by surgery and definitive chemoradiotherapy for survival in patients with resectable esophageal squamous cell carcinoma (JCOG2305A).

417 Background: Neoadjuvant triplet chemotherapy followed by surgery (Neo-S) has become the standard treatment for resectable esophageal squamous cell carcinoma (ESCC) based on the results of JCOG1109. However, definitive chemoradiotherapy (CRT) remains an option for organ preservation with curative intent. This analysis aimed to explore subgroups of patients undergoing CRT, including salvage treatment, to identify those with survival outcomes potentially equivalent to Neo-S. Methods: Pooled data from two clinical trials of patients with resectable (T1N1-3M0 and T2-3NanyM0) ESCC. JCOG0909 was a single-arm trial that evaluated upfront CRT consisting of 5-FU (1000 mg/m 2 on day1-4, 29-32) and cisplatin (80 mg/m 2 on day1, 29) combined with radiotherapy at a dose of 50.4 Gy, including salvage treatment. If there was no progression at the time of salvage treatment, it was not regarded as an event for progression-free survival (PFS) in JCOG0909. JCOG1109 compared neoadjuvant treatment with doublet chemotherapy, triplet chemotherapy, and doublet chemotherapy with radiotherapy followed by surgery. The patients were enrolled in JCOG0909 between 2010 and 2014 and in JCOG1109 between 2012 and 2018. Subgroup analyses of clinical data, including tumor location, cT, cN, and clinical stage, were conducted on overall survival (OS) and PFS using Cox proportional hazards regression models for patients with JCOG0909 and JCOG1109. When a subgroup with a multivariable hazard ratio (HR) of more than 0.91 was detected, CRT including salvage treatment was considered not to be inferior to Neo-S in that subgroup. Results: Ninety-three patients in the CRT group from JCOG0909 and 196 patients in the Neo-S group from the triplet chemotherapy arm of JCOG1109 were included in this analysis. Although there were no significant differences, PFS and OS tend to be better in the Neo-S group than in the CRT group (PFS, HR 0.72, 95% confidence interval [CI] 0.50-1.03; OS, HR 0.89, 95% CI 0.59-1.36). For patients with Ut/Mt or cT1-2 disease, OS in the Neo-S group had a HR of 0.91 or more compared with those in the CRT group (Table). Conclusions: Subgroups in which OS after CRT including salvage treatment was not inferior to that of Neo-S were identified. Hazard ratios of Neo-S to CRT by subgroups in multivariable Cox regression. Progression-free survival Overall survival Subgroups Hazard ratio 95% confidence interval Hazard ratio 95% confidence interval Ut/Mt 0.85 0.56-1.28 1.13 0.70-1.83 Lt 0.45 0.21-0.97 0.44 0.19-1.00 cT1-2 0.88 0.46-1.68 1.45 0.65-3.24 cT3 0.66 0.42-1.02 0.72 0.44-1.16 cStage IB+II 0.79 0.45-1.36 1.06 0.56-2.00 cStage III 0.75 0.45-1.23 0.92 0.52-1.62 Overall 0.72 0.50-1.03 0.89 0.59-1.36 Ut upper thoracic esophagus, Mt middle thoracic esophagus, Lt lower thoracic esophagus.

Radiosensitizing Capacity of Fenofibrate in Glioblastoma Cells Depends on Lipid Metabolism

Despite advances in multimodal therapy approaches such as resection, chemotherapy and radiotherapy, the overall survival of patients with grade 4 glioblastoma (GBM) remains extremely poor (average survival time <2 years). Altered lipid metabolism, which increases fatty acid synthesis and thereby contributes to radioresistance in GBM, is a hallmark of cancer. Therefore, we explored the radiosensitizing effect of the clinically approved, lipid-lowering drug fenofibrate (FF) in different GBM cell lines (U87, LN18). Interestingly, FF (50 μM) significantly radiosensitizes U87 cells by inducing DNA double-strand breaks through oxidative stress and impairing mitochondrial membrane integrity, but radioprotects LN18 cells by reducing the production of reactive oxygen species (ROS) and stabilizing the mitochondrial membrane potential. A comparative protein and lipid analysis revealed striking differences in the two GBM cell lines: LN18 cells exhibited a significantly higher membrane expression density of the fatty acid (FA) cluster protein transporter CD36 than U87 cells, a higher expression of glycerol-3-phosphate acyltransferase 4 (GPAT4) which supports the production of large lipid droplets (LDs), and a lower expression of diacylglycerol O-acyltransferase 1 (DGAT1) which regulates the formation of small LDs. Consequently, large LDs are predominantly found in LN18 cells, whereas small LDs are found in U87 cells. After a combined treatment of FF and irradiation, the number of large LDs significantly increased in radioresistant LN18 cells, whereas the number of small LDs decreased in radiosensitive U87 cells. The radioprotective effect of FF in LN18 cells could be associated with the presence of large LDs, which act as a sink for the lipophilic drug FF. To prevent uptake of FF by large LDs and to ameliorate its function as a radiosensitizer, FF was encapsulated in biomimetic cell membrane extracellular lipid vesicles (CmEVs) which alter the intracellular trafficking of the drug. In contrast to the free drug, CmEV-encapsulated FF was predominantly enriched in the lysosomal compartment, causing necrosis by impairing lysosomal membrane integrity. Since the stability of plasma and lysosomal membranes is maintained by the presence of the stress-inducible heat shock protein 70 (Hsp70) which has a strong affinity to tumor-specific glycosphingolipids, necrosis occurs predominantly in LN18 cells having a lower membrane Hsp70 expression density than U87 cells.In summary, our findings indicate that the lipid metabolism of tumor cells can affect the radiosensitizing capacity of FF when encountered either as a free drug or as a drug loaded in biomimetic lipid vesicles.

An exploratory study of serum creatine kinase as a prognostic marker for patients with resectable pancreatic cancer: looking into the relationship with body composition

BackgroundAmong cancer patients, pancreatic cancer patients have the highest rate of sarcopenia, which is a critical prognostic factor. Serum creatine kinase (CK) is closely related to skeletal muscle mass and has been reported to decline with the progression of cancer. This study investigated whether preoperative serum CK is associated with the survival of patients with pancreatic cancer.MethodsData were obtained from patients with pathologically confirmed pancreatic cancer between June 2016 and March 2022. The prognostic significance of CK was analyzed based on sex-stratified groups. The Kaplan-Meier method was used to compare overall survival (OS) and disease-free survival (DFS). Multivariate Cox proportional hazards models were used to determine prognostic factors. Body composition was analyzed based on preoperative abdominal CT images to explore the sex-specific associations between skeletal muscle area (SMA) and serum CK levels.ResultsA total of 166 patients were included in this study. Sarcopenia was presented in 70 patients (42.2%). A low serum CK level showed a significant correlation with the diagnosis of sarcopenia in male patients (P = 0.026). The levels of CK did not predict the outcome in female patients, while a low preoperative CK was notably linked to shorter OS in male patients (median OS: 15 months vs. 33 months, P = 0.011; median DFS: 5 months vs. 14 months, P = 0.007). Multivariate analyses further confirmed the effect of CK in predicting OS (CK>44 IU/L, HR:0.226, 95% CI:0.107–0.478, P < 0.001) and DFS (CK>44 IU/L, HR:0.272, 95% CI:0.139–0.529, P < 0.001) of male patients. Correlation analysis revealed a significant association between SMA and CK levels in male patients (r = 0.225, P = 0.025), and such a correlation was not observed in female patients (r = 0.088, P = 0.478).ConclusionThe pretherapeutic CK may represent a simple marker for predicting poor survival in male patients with resectable pancreatic cancer, thereby aiding in the selection of therapeutic strategies.

Progressive natural killer cell dysfunction in advanced-stage clear-cell renal cell carcinoma and association with clinical outcomes.

Natural killer (NK) cells are important contributors to antitumor immunity in clear-cell renal cell carcinoma (ccRCC). However, their phenotype, function, and association with clinical outcomes in ccRCC remain poorly understood. We analyzed single-cell RNA sequencing data from 13 primary tumors, 1 localized tumor extension, and 1 metastasis from ccRCC patients at different clinical stages. For each primary tumor specimen, paired normal kidneys were also analyzed. Differential gene expression analysis was carried out to investigate NK cell phenotypes and to derive a gene expression signature. Gene signatures from NK cell subclusters of interest were used to interrogate bulk transcriptomic datasets and expression with clinical outcomes. Finally, tumor-infiltrating NK cell function (cytokine production and cytotoxicity) was assessed by isolation of live NK cells from ccRCC tissue, co-culture with K562 target cells, and measurement of cytokine production (interferon-γ) and cytotoxicity (CD107a) markers by flow cytometry. Single-cell transcriptomic data were analyzed from 13 patients with ccRCC (tumor/normal kidney), resulting in 21 139 NK cells. Clustering analysis revealed six NK cell subsets. Bright-like NK cells were significantly enriched in advanced ccRCC compared with localized ccRCC and normal kidney, expressed markers of tissue residency (ZNF683/Hobit, ITGA1/CD49a, CD9, ITGAE/CD103), and had decreased expression of cytotoxicity genes (GZMB/Granzyme-B, PRF1/perforin). In independent cohorts (The Cancer Genome Atlas ccRCC cohort, CheckMate 025), a gene expression score representing this dysfunctional NK cell phenotype was enriched in advanced ccRCC and was associated with worse overall survival. Functional interrogation of tumor-infiltrating NK cells from ccRCC confirmed that tumor-resident CD49a+CD9+ NK cells had impaired cytotoxicity compared with CD49a-CD9- NK cells. A dysfunctional, tumor-resident NK cell phenotype was enriched among patients with metastatic disease and associated with worse survival in patients with advanced ccRCC across multiple patient cohorts. Restoration of NK cell function (via cytokine stimulation or NK cell engineering) could provide a novel avenue for therapeutic intervention against ccRCC.

Abdominal myosteatosis measured with computed tomography predicts poor outcomes in patients with glioblastoma.

Alterations in cellular metabolism affect cancer survival and can manifest in metrics of body composition. We investigated the effects of various body composition metrics on survival in patients with glioblastoma (GBM). We retrospectively analyzed patients who had an abdominal and pelvic computed tomography (CT) scan performed within 1 month of diagnosis of GBM (178 participants, 102 males, 76 females, median age: 62.1 years). Volumetric body composition metrics were derived using automated CT segmentation of adipose tissue, skeletal muscle, and aortic calcification from L1 to L5. Univariable and multivariable Cox proportional hazards models were performed separately in males and females using known predictors of GBM overall survival (OS) as covariates. A sex-specific composite score of predisposing and protective factors was constructed using the relative importance of each metric in GBM OS. Higher skeletal muscle volume and lower skeletal muscle fat fraction were associated with better OS in the entire dataset. A robust and independent effect on GBM OS was seen specifically for fraction of inter/intramuscular adipose tissue to total adipose tissue after correction for known survival predictors and comorbidities. Worse OS was observed with increased abdominal aortic calcification volume in both sexes. There was a significant difference in GBM OS among participants stratified into quartiles based on sex-specific composite predisposing and protective scores. The relationship between body composition and GBM OS provides an actionable advancement toward precision medicine in GBM management, as lifestyle and dietary regimens can alter body composition and metabolism and from there GBM survival.

Transarterial chemoembolization (TACE) combined with camrelizumab and apatinib versus TACE alone in the treatment of unresectable hepatocellular carcinoma eligible for embolization: A multicenter, open-label, randomized, phase 2 study (CAP-ACE).

LBA522 Background: Transarterial chemoembolization (TACE) has been established as a standard treatment for hepatocellular carcinoma (HCC) eligible for embolization. Combining immunotherapy and tyrosine kinase inhibitors (TKIs) with TACE can potentially enhance antitumor activity by activating the immune system and inhibiting tumor neovascularization. This study investigated whether the addition of camrelizumab and apatinib to TACE could bring better survival benefits. Methods: This open-label, randomized phase 2 study (NCT04559607) was conducted at 23 sites in China. Patients with unresectable HCC eligible for embolization were randomly assigned to receive either TACE combined with camrelizumab (200 mg once every 3 weeks) and apatinib (250 mg once daily; TACE-CA) or TACE alone. The stratification factors for randomization included vascular invasion (yes vs. no), prior use of TKIs (yes vs. no), and number of prior TACE (0 vs. 1-2). Prior immunotherapy was not allowed. The primary endpoint was progression-free survival (PFS) assessed by investigators according to the Response Evaluation Criteria In Cancer of the Liver (RECICL), analyzed in intention-to-treat population. Results: Between Dec 28, 2020 and Oct 29, 2023, 200 patients were randomized (100 in each group). Median age was 58.5 years (IQR, 51.5-65) and 57.0 years (IQR, 51-65.5) in the TACE-CA and TACE groups, respectively; most patients had Barcelona Clinic liver cancer (BCLC) stage B-C disease (86.0% and 86.0%). As of October 16, 2024, the median follow-up duration was 13.6 months (IQR, 8.2-20.5). Median PFS per RECICL was significantly longer in the TACE-CA group compared with the TACE group (11.0 months [95% CI, 8.8-13.8] vs. 3.1 months [95% CI, 2.0-4.1]; hazard ratio, 0.3, P&lt;0.0001). The objective response and disease control rates were 65.0% (95% CI, 54.8-74.3) and 87.0% (95% CI, 78.8-92.9) in the TACE-CA group and 30.0% (95% CI, 21.2-40.0) and 63.0% (95% CI, 52.8-72.4) in the TACE group, respectively. Overall survival data are immature. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 76.6% (72/94) of patients with TACE-CA and 24.3% (25/103) of patients with TACE. The most common grade ≥3 TRAEs were increased aspartate aminotransferase (AST; 29 [30.9%]), increased alanine aminotransferase (ALT; 23 [24.5%]), hypertension (13 [13.8%]), and decreased platelet count (11 [11.7%]) in the TACE-CA group, and increased ALT (16 [15.5%]) and increased AST (15 [14.6%]) in the TACE group. Conclusions: The addition of camrelizumab and apatinib to TACE can significantly prolong progression-free survival in patients with unresectable HCC eligible for embolization, with a manageable safety profile. Clinical trial information: NCT04559607 .

Racial, gender and socioeconomic disparities in survival outcomes of hepatocellular carcinoma.

526 Background: Hepatocellular carcinoma (HCC) is the sixth most commonly occurring cancer worldwide, with mortality rates increasing globally, particularly in the Western world. The 5‐year survival rate of persons with HCC is less than 20%. It is, therefore, essential to investigate the extent to which social determinants of health influence survival outcomes. In this study, we explored the effect of gender, race/ethnicity and socioeconomic factors on survival outcomes among patients with HCC in the United States. Methods: We extracted data on patients with a histologic diagnosis of hepatocellular carcinoma from the Surveillance, Epidemiology and End Result (SEER) Registry from 2000-2021. The primary outcome of interest was the cause-specific survival of these patients. According to the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) system, the histological code of HCC is 8170/3. We excluded patients of missing or unknown race, income, location, and patients outside the years of study. Cox proportional hazard regression (SPSS) was utilized to determine the association between patients' race/ethnicity, gender, annual median income, location and cause-specific survival. Results: 80,445 met the criteria and were included in our study. Gender proved to be a predictor of survival; compared to females, males had worse outcomes, with males HR 1.040 (95% CI; 1.020-1.060, p = &lt;0.001). Race was a predictor of survival outcomes. Using American Indian/Alaska Native as our reference, Asian/Pacific Islander HR 0.847 (95% CI; 0.790-0.90, p = &lt;0.001), Black HR 1.019 (95% CI; 0.950-1.093, p = 0.603), White HR 0.955 (95% CI; 0.893-1.023, p = 0.186). We also analyzed the effects of socioeconomic factors on survival. Patients with higher annual median income had better outcomes. &gt;$120000 HR 0.817 (95% CI; 0.783-0.851, p = &lt;0.001) while patients with lower annual median income had worse outcomes &lt; $40000 HR 1.217 (95% CI; 1.134-1.305, p &lt; 0.001). The effect of location on survival was not significant. Compared to non-metropolitan areas, metropolitan areas HR 0.988 (95% CI; 0.971–1.004, p = 0.138). Conclusions: Race/ethnicity, income and gender disparities all played a significant role in cause-specific survival in patients with HCC, with improved survival observed in females, Asians and patients with higher annual median income. More efforts are needed to bridge these survival disparities.

Development and regulatory approval of a new systemic targeted therapy for advanced hepatocellular carcinoma.

613 Background: There are no commercially available devices for the treatment of patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy. We have identified tumor-specific modulation frequencies in patients with advanced hepatocellular carcinoma. We exposed patients to radiofrequency electromagnetic fields, which are amplitude-modulated from 0.1 Hz to 100 kHz and measured changes in pulse pressure. Frequencies eliciting measurable changes in pulse pressure were selected as tumor-specific frequencies. Methods: Treatment is administered to patients with advanced hepatocellular carcinoma by means of a battery-operated portable device emitting 27 MHz radiofrequency electromagnetic fields, which are amplitude-modulated at hepatocellular carcinoma frequencies. The device is connected to a coaxial cable ending with a spoon-shaped antenna placed on the anterior part of the patient's tongue during treatment. Treatment is administered three times a day for one hour. Results: A total of 69 patients with advanced hepatocellular carcinoma received treatment with the TheraBionic device until progression or death. The median overall survival of patients who received treatment with the TheraBionic device after failing 1st line and 2nd line therapy was 9.15 (95% CI 1.6-34.8) months and the median overall survival of Child-Pugh A patients was 9.5 months, which are comparatively longer than the 7.8 months pooled estimated medians of the placebo arms of 11 randomized 1st line and 2nd line placebo-controlled studies assessing the safety and efficacy of new agents for the treatment of Child-Pugh A advanced HCC (Llovet, Montal et al., J Hepatol 2019). We also analyzed the survival of patients who had received two lines of systemic therapy and did not receive any additional cancer treatment while and after receiving treatment with the TheraBionic device. The median OS of these patients was 9.8 months and the median OS of the Child-Pugh A patients was 17.2 months, which are comparatively longer than the 7.74 months pooled estimated medians of the placebo arms of the above cited 11 randomized studies. To assess unknown device-related adverse events, we assessed patient reported symptoms using the same scale in the SHARP and Asian Pacific Sorafenib studies. The incidence of any grade adverse events among Child-Pugh A who received treatment with the TheraBionic device was not different from the Placebo group of the SHARP and Asian Pacific Sorafenib studies. There were no NCI Grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient developed grade 1 fatigue. Conclusions: The data presented here provide reasonable assurance of safety and probable benefit in patients with advanced hepatocellular carcinoma who have failed 1st line and 2nd line therapy: https://www.fda.gov/medical-devices/recently-approved-devices/therabionic-p1-h220001 .

Correlation of tumoral collagen width with overall survival and tumoral collagen straightness with distant recurrence-free survival in patients with pancreatic ductal adenocarcinoma.

779 Background: Quantitative measurements of fibrillar collagen characteristics has been shown to correlate with survival in several types of malignancy. The aim of this study was to determine whether these characteristics correlate with survival in pancreatic ductal adenocarcinoma. Methods: Patients who underwent pancreatic resection for pancreatic ductal adenocarcinoma at an Allegheny Health Network hospital between 1/1/2019 and 12/31/2023, and for whom archived formalin-fixed paraffin-embedded tumor tissue was available, were included in the study. Clinical and pathologic characteristics were collected from the patient's electronic medical record. Survival data included overall survival (OS), local recurrence-free survival (RFS), and distant RFS. One section of tumor per patient was stained with Picrosirius Red and a representative digital image was obtained with a camera attached to a microscope at 100x magnification. Each image was analyzed with CT-FIRE software to determine averages of collagen fiber width, length, straightness, and angle. Descriptive statistics were initially computed. Log-rank tests were also conducted to compare the OS rate and RFS rate between four different groups (width, length, straightness, angle). Each group was divided into high and low groups, using the mean as cutoff. In the end, multivariate Cox regression was conducted by controlling the confounders including sex, perineural invasion, lymphovascular invasion, and presence of lymph node metastasis to examine the hazard ratios of OS, local RFS, and distant RFS for the four collagen fiber metrics. All statistical analyses were performed via SAS 9.4 under alpha level .05. Results: One hundred three patients met the inclusion criteria. Based on the results of log-rank test, OS was significantly different between high and low collagen width groups, p = .0251. The lower width group had higher survival rate than the upper width group. Also, distant recurrence-free survival was significantly different between high and low collagen straightness groups, p = .0053. The lower straightness group had higher distant RFS rate than upper group. The results of multivariate Cox regression were consistent with the Kaplan-Meier curves. Compared to the high collagen width group, the low collagen width group had a 57% lower chance of dying, hazard ratio = 0.43, 95% CI [0.23, 0.78], p = .0056. The low collagen straightness group had a 60% lower chance of distant recurrence than the high collagen straightness group, hazard ratio = 0.40, 95% CI [0.19, 0.85], p =.0163. Conclusions: Quantitative collagen fiber metrics could help identify patients with resected pancreatic adenocarcinoma who are at risk of earlier death and distant recurrence.

A protocol for pretreatment testing for antibodies to galactose-alpha-1,3-galactose to mitigate the risk of cetuximab hypersensitivity reactions.

115 Background: Cetuximab has been shown to improve survival in patients with KRAS wildtype metastatic colorectal cancer. However, high rates of hypersensitivity reactions (HSRs) limit its use, with HSR rates up to 10-20%. A major driver of cetuximab HSR is from pre-formed antibody response to galactose-1,3-alpha-galactose (alpha-gal). Evidence from retrospective studies supports alpha-gal pre-screening in this setting. We are the first to report on the impact of prospective alpha-gal antibody screening on cetuximab HSR. Methods: Records were reviewed across three medical oncology centres that have adopted alpha-gal antibody screening measures. Data for patients with metastatic colorectal cancer treated with cetuximab were retrieved. All centres assessed alpha-gal antibody status using the ImmunoCAP ELISA assay. Due to lack of a shared screening approach across study sites, a pre-determined protocol was retrospectively applied to all cases. This protocol allowed cetuximab administration if alpha-gal levels were ≤0.1 kUA/L, but prohibited it if alpha-gal levels were &gt;0.1 kUA/L in favour of panitumumab administration. Patients were allocated to either the Protocol Applied or Protocol Not Applied cohorts based on protocol requirements being met. The primary outcome between these patient groups was the incidence of cetuximab HSRs. Results: Of 254 assessable patients, 39 underwent the pre-treatment screening protocol. Of the Protocol Applied group, 3% (n=1/38) experienced a cetuximab HSR compared to 16% (n=35/215) in the Protocol Not Applied group (Odds ratio (OR) 7.16; 95% CI 1.13–299.61, p =0.02). Patients with alpha-gal antibody titres &gt;0.1 kUA/L were more likely to experience a cetuximab HSR (OR 69.71; 95% CI 5.18–4296.81, p =0.0001). Conclusions: Pre-treatment screening for alpha-gal antibodies significantly reduces the incidence of cetuximab HSRs. A testing threshold of 0.1 kUA/L is effective in identifying patients at risk. Implementing this protocol can improve the safety of cetuximab therapy in high-risk populations.

Effect of marital status and race on survival of patients with well differentiated neuroendocrine tumors (NETs).

654 Background: Socioeconomic status factors (SES) such as marital status, income, and race can influence and enhance disparities in cancer incidence and outcomes. Marriage has documented positive impacts on overall survival of numerous cancer types. Consequences of divorce have been less explored. The unique indolent, secretory nature of NETs may be differentially affected by SES factors. This study identifies implications of marital status and sex on 5-year survival rates of different racial groups diagnosed with NETs within the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2020 while controlling broadly for the type of treatment received. Methods: Within the SEER data base patients with reported sex, race, marital status and treatment who were diagnosed with well differentiated NETs were selected excluding carcinomas. Relative and disease specific 5-year survival analyses were calculated with 95% confidence intervals and age standardized. Three groupings were analyzed single, separated/divorced/widowed and domestic-partner/married. Results: For all races and sexes, relative survival for individuals in a union was higher than those who were single, or separated, divorced/widowed [86.9% (CI 86.1% - 87.7%); 79.3% (77% to 81.3%); and 79.2% (78% to 80.3%) respectively]. When individuals of each marital status group were compared by matching sex and race, there were no significant differences in relative survival. But males of any race who left a union had lower chances of survival than corresponding females [72.4% (69.7% to 74.9%) vs 81.6% (80.3% to 82.8%)]. As expected, all groupings who received surgical treatment had a higher relative survival than those who did not. Those who received surgical treatment while in a partnership had a higher relative survival then those who were separated [94.5% (93.6% to 95.3%) vs 88.7% (87.3% to 89.9%)]. All marital groupings who underwent surgery or did not, had comparable relative survival between races; except, black individuals in a partnership had improved outcomes compared to the white population. More specifically, when accounting for race, sex, marital status and treatment received, black men who did not undergo surgery had a higher relative survival compared to white men [69.9% (62.2% to 76.3%) vs 59.4% (56.6% to 62.1%)]. All the same conclusions were statistically significant for disease specific survival. Conclusions: Due to NETs slow growing nature SES factors play a major role in the care of patients living with them. Our findings demonstrate generally, irrespective of race, sex, or surgical treatment, being involved in a union is advantageous, showing a protective effect on patient survival, while parting from a union could be deleterious as it is tied to less favorable outcomes. These findings underscore the importance of considering these factors in treatment and care strategies.

Prognostic value of circulating and tumor microenvironmental biomarkers in endometrial cancer.

Endometrial cancer (EC) is one of the three most common gynecological malignancies. Thus, it is estimated that the mortality rates due to this disease will increase. Our aim is to study the immune microenvironment in all ECs together with Hematoxylin Eosin (H&E), immunohistochemical (IHC) and Biochemical parameters (NLR) and to evaluate their contribution to prognosis by comparing them with each other. A total of 340 EC patients were included in the study. PDL-1 immunohistochemical stain was applied to blocks prepared from representative tumor tissues by Tissue Microarray method. Tumor- infiltrating lymphocytes and neutrophils were also scored with Hematoxylin Eosin stain. The NLR values calculated from peripheral blood. The effects of all parameters on survival, recurrence/metastasis were statistically evaluated. Regarding TIL Scores, patients with higher TIL scores were found to have longer disease-free survival and total survival. In patients with high TIN scores, disease-free survival and overall survival were shorter. (p < 0.001) The overall survival of patients with PDL-1 negative was found to be longer. (p: 0.07). In terms of the effect on OS, an NLR cut-off value of 2.72 was determined (specificity 38.89 %, sensitivity 82.57 %, AUC 0.65). OS was 77.11 months ( ± 0.04, 95 % CI: 71.8-81.9) in the patients with NLR value slower than 2.72 and 76.5 months ( ± 1.3, 95 % CI: 36.3-63.7) in those with NLR ≥ 2.72 (p: 0.001). In this study, all patients of EC with high TIL scores, low TIN scores, and with PD-L1 negativity exhibited significantly longer survival times. TIN appears to be a highly valuable parameter in terms of both OS and PFS, particularly compared to TIL and PD-L1. This research represent a pioneering study for future studies involving larger samples in the context of being able to use different parameters in predicting prognosis and treatment in patients with EC.

Comparative efficacy of TAS-102 and chemotherapy rechallenge in the third-line setting and beyond in patients with advanced colorectal cancer: A retrospective study.

78 Background: The optimal approach to third line therapy for patients with metastatic colorectal cancer remains a subject of debate. Options include Trifluridine/Tipiracil (TAS-102), TAS-102 with bevacizumab, regorafenib, chemotherapy rechallenge with or without an anti-EGFR agent, or fruquintinib. This study aims to evaluate the efficacy of standard of care TAS-102, TAS-102 with bevacizumab, or regorafenib versus chemotherapy rechallenge in patients with metastatic colorectal cancer in the third line setting and beyond. Methods: We conducted a retrospective analysis of patients with metastatic colorectal cancer who received either TAS-102 with or without bevacizumab, regorafenib or chemotherapy rechallenge with or without an anti-EGFR agent between 2018 and 2023, at the Ministry of National Guard for Health Affairs in Riyadh, Saudi Arabia. Patients received such agents in the third line setting and beyond. Results: A total of 75 patients were included in this study, with 39 patients receiving TAS-102 with or without bevacizumab, or regorafenib, and 36 receiving chemotherapy rechallenge. The median patient age was 58 years (range 28-81), with the majority being males at 55%. Among the chemotherapy rechallenge group, 31% were treated with cetuximab and 6% had panitumumab rechallenge, some of which were guided by cell free DNA liquid biopsy testing. In the other group, 66% received regorafenib, 26% TAS-102 alone, and 8% TAS-102 with bevacizumab. At the time of analysis, 56% of patients had passed away. Median overall survival for patients who received TAS-102 with our without bevacizumab, and regorafenib in the third line setting was found to be 13.1 months. Whereas for patients who received chemotherapy rechallenge, their median overall survival was 19.5 months. Conclusions: Patients with metastatic colorectal cancer who received chemotherapy rechallenge in the third line setting survived longer compared with patients who received TAS-102 with or without bevacizumab, or regorafenib.

Clinical-pathological characteristics, follow-up, and survival of patients with early-onset vs late-onset colorectal cancer: Institutional experience in Argentina.

82 Background: The incidence of colorectal cancer (CRC) in young adults aged 50 or younger (Early Onset - EO) is increasing worldwide, while in patients over 50 years old (Late Onset - LO), it is declining. The objective is to compare the clinicopathological characteristics, time to diagnosis, and survival between Early Onset (EO) and Late Onset (LO) patients diagnosed with colorectal cancer (CRC). Methods: The sample was described using measures of central tendency and dispersion for continuous numerical variables and percentages for categorical variables. Clinical characteristics between Early Onset (EO) and Late Onset (LO) groups were compared using the Student’s t-test or Chi-square test. Kaplan-Meier curves and the Log-Rank Test were utilized to analyze mortality time. For multivariable analysis, a Cox regression model was applied. A p-value of less than 0.05 was considered statistically significant. The analysis was performed using RStudio. Results: A total of 460 patients were evaluated, with 343 diagnosed with colon adenocarcinoma and 117 with rectal cancer. Patients were grouped into two categories: the LO group with 408 (88.6%) patients and a mean age of 69.3 (8.60 SD) years, and the EO group with 52 (11.3%) patients and a mean age of 41.9 (6.23 SD) years. The EO group presented a higher percentage of patients with a PS of 0 compared to the LO group. In the EO group, there was a predominance of left-sided colon cancer (40.4% vs. 40.0%) and rectal cancer, especially in the middle and lower regions (30% vs. 18.8%), with disease diagnosed at stage III (26.9% vs. 26.5%) and IV (5.8% vs. 4.4%) compared to the LO group. Molecular testing for KRAS, NRAS, and BRAF mutations was more frequent in the EO group (19.2%, 3.8%, and 3.8%, respectively) compared to the LO group, as well as mismatch repair (MMR) status at 9.6% in the EO group vs. 6.9% in the LO group. The median time to diagnosis was 186 days in the LO group and 341 days in the EO group (p=0.21). Follow-up was 858 days in the LO group and 725 days in the EO group (p=0.18); while mortality was 200 (49.0%) in the LO group and 24 (46.2%) in the EO group, with a median survival of 1193 days for the LO group and 1414 days for the EO group, respectively (p=0.7). PS and stage were the most influential prognostic factors for mortality. Conclusions: In the comparison, the EO group showed a higher incidence of left-sided colon and rectal cancers, more advanced stages, better PS, and a greater number of molecular alterations, with a longer time to diagnosis and shorter follow-up. Although these differences were not statistically significant, they highlight the need to optimize prevention strategies and genetic counseling. Additional studies with a larger number of EO patients in real-life contexts are needed to generate more evidence that can improve clinical decision-making.

Immune-related adverse events as prognostic biomarkers in recurrent or metastatic nasopharyngeal carcinoma receiving PD-L1 inhibitor: A post-hoc analysis of the multicenter, single-arm, phase 2 study.

Immune-related adverse events (irAEs) have been associated with better therapeutic outcomes in patients receiving immune checkpoint inhibitors (ICIs) across various cancers. This study investigates the association between irAEs and ICI outcomes in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). A post hoc analysis was performed on 153 patients with R/M NPC who received anti-PD-L1 inhibitors between February 26, 2019, and January 13, 2021. These patients were enrolled in a multicenter, single-arm, phase 2 clinical trial, which represents the largest study to date evaluating anti-PD-L1 therapy in previously treated R/M NPC. Patients who experienced irAEs had significantly higher overall response rates (ORR) and diseade control rates (DCR) compared to those without irAEs (31.2% vs. 17.1%, p=0.039; 66.7% vs. 44.8%, p=0.017). Additionally, the median progression-free survival (PFS) was longer in patients with irAEs (129days vs. 56days, p=0.007). Patients with endocrine-related irAEs exhibited higher DCR (71.8% vs. 46.2%, p=0.012), and longer PFS (144days vs. 69days, p=0.02) and overall survival (OS: 746days vs. 438days, p=0.02). In contrast, patients with grade≥3 irAEs or thoserequiring systemic steroid therapy had shorter median OS (179days vs. 466days, p=0.03; 166days vs. 462days, p=0.02). The occurrence of irAEs, particularly those involving the endocrine system, is associated with enhanced efficacy of anti-PD-L1 therapy and extended survival in patients with R/M NPC, highlighting their potential as prognostic biomarkers.

Low muscle mass in the internal medicine ward: Prevalence and survival implications

BackgroundLow muscle mass is common in hospitalized patients. It is associated with adverse clinical outcomes. Reported prevalence varies widely due to non-universally accepted diagnostic criteria and the heterogeneity of the populations studied. Non-surgical ill patients are underrepresented in the literature. AimsTo estimate the prevalence of low muscle index and its impact on survival in patients admitted to an internal medicine unit. MethodsWe prospectively enrolled patients with abdominal CT scans on admission to the Internal Medicine ward. We assessed muscle mass index (L3MI) at the level of the L3 lumbar vertebra. The primary outcome was to estimate the prevalence of low muscle mass on admission. Secondary outcomes were to determine the relationship of low L3MI with hospital mortality, length of stay, nosocomial infections, and hospital readmission. ResultsOne hundred and seven patients were included. The prevalence of low L3MI was 46.7%. An L3MI of 46.3 cm2/m2 in men and 40.9 cm2/m2 in women predicted death at one year with a sensitivity of 66% and a specificity of 78% (AUC = 0.62 [95% CI 0.38–0.86]) and 69 and 66% (AUC of 0.63 [95% IC 0.47–0.78]), respectively. In-hospital mortality, death at 60, 90, and 360 d, and hospital readmission were significantly higher in patients with low L3MI. ConclusionAlmost half of the patients admitted to an internal medicine ward have low muscle mass index. The cutoff point of 40.9 cm2/m2 in females and 46.3 cm2/m2 in males predicts relevant clinical variables. We established the better L3MI cutoff value to predict 12-month mortality.

A multi-institutional retrospective study evaluating clinical outcomes and prognostic factors in patients with metastatic appendiceal adenocarcinoma.

69 Background: Appendiceal adenocarcinoma (AA), a rare cancer, has been reported to have high incidences of mucinous type histology, peritoneal metastasis, and relatively good prognosis. However, its chemotherapeutic efficacy and prognostic factors is not well known. Methods: We collected patients with metastatic AA treated with chemotherapy between February 2005 and March 2023 in two high volume cancer centers in Japan. We retrospectively analyzed the clinical outcomes of the chemotherapy of patients with metastatic AA and the clinical factors associated with treatment efficacy and prognosis by multivariate analysis. Results: A total of 66 patients with a median age of 54 years, were enrolled. 40 patients (60.6%) received an oxaliplatin-based regimen in combination with bevacizumab. The response rate was 22.0% and the disease control rate was 87.8%. With median follow-up period was 15.5 months [1.9-103.1], median progression-free survival (PFS) was 10.9 months [95% CI: 7.2-15.2] and median overall survival (OS) was 23.0 months [95% CI: 19.6-35.8]. 77.4% of patients received subsequent chemotherapy. In multivariate analysis, pretreatment carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) were associated with significantly shorter PFS (HR: 2.93, P = 0.0049). Presence of primary tumor (HR:2.50, P = 0.015), ECOG performance status (PS) ≥1 (HR: 2.67, P = 0.0091), moderate to massive ascites (HR: 3.06, P = 0.0043) and high tumor marker levels (HR: 2.46, P = 0.026) were associated with significantly shorter OS. Classifying the patients by number of these prognostic factors for OS into three groups (0, 1-2, and 3-4), the group with prognostic factors (1-2 or 3-4) had a significantly shorter prognosis compared to the group without any these factors (0 vs 1-2: HR: 4.70, P = 0.038, 0 vs 3-4: HR: 17.6, P &lt; 0.01). In addition, the group with 3-4 prognostic factors had relatively lower rate of subsequent chemotherapy ratio than the group without these factors (66.7% vs 100%, P = 0.25). Conclusions: We confirmed our treatment outcomes were consistent with previous studies and elevation of tumor markers presence of primary tumor, ECOG PS ≥1, moderate to massive ascites were significantly associated with survival in patients with metastatic AA.